Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001068644 | SCV001233769 | uncertain significance | Atrial septal defect 7 | 2023-07-25 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NKX2-5 protein function. ClinVar contains an entry for this variant (Variation ID: 862013). This variant has not been reported in the literature in individuals affected with NKX2-5-related conditions. This variant is present in population databases (rs372282873, gnomAD 0.008%). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 212 of the NKX2-5 protein (p.Pro212Arg). |
| Gene |
RCV001593249 | SCV001817066 | uncertain significance | not provided | 2019-07-05 | criteria provided, single submitter | clinical testing | Reported in association with congenital heart defects (Abdul Samad et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Identified in individuals referred for DCM genetic testing at GeneDx; however, one of these probands harbored a pathogenic variant in another DCM-related gene; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 211673; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 27152669) |
| Fulgent Genetics, |
RCV002482121 | SCV002775869 | uncertain significance | Atrial septal defect 7; Conotruncal heart malformations; Hypothyroidism, congenital, nongoitrous, 5; Tetralogy of Fallot; Ventricular septal defect 3; Hypoplastic left heart syndrome 2 | 2021-07-26 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004639456 | SCV005138838 | uncertain significance | Cardiovascular phenotype | 2024-04-06 | criteria provided, single submitter | clinical testing | The p.P212R variant (also known as c.635C>G), located in coding exon 2 of the NKX2-5 gene, results from a C to G substitution at nucleotide position 635. The proline at codon 212 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |